After excluding frequently sampled intravenous glucose tolerance test failures (n = 4) and extreme outliers (n = 5), 18 subjects in the treatment group and 15 subjects in the control group were finally analyzed. The institutional review board of Seoul National University Hospital approved this study.

To summarize, we have demonstrated for the first time that vitamin K2 supplementation for 4 weeks increased insulin sensitivity in healthy young men, which seems to be related to increased cOC rather than modulation of inflammation. Small sample size limits firm interpretation on β-cell function. Our results are consistent with previous studies that demonstrated improved glucose intolerance or relieved insulin resistance by treatment with vitamin K1 (3) or vitamin K2 (4), respectively. We conclude that unlike in rodents, cOC rather than ucOC may be the endocrine hormone that increases insulin sensitivity in humans. Although our study could not provide the underlying mechanism, we speculate that cOC or vitamin K could modulate adipokines or inflammatory pathways other than the IL-6 pathways. Alternatively, cOC can directly regulate glucose disposal at skeletal muscle or adipose tissues. Further studies to elucidate the mechanism of action are warranted.

Acknowledgments

No potential conflicts of interest relevant to this article were reported.

H.J.C. researched data, contributed to discussion, wrote the manuscript, and reviewed and edited the manuscript. J.Y. researched data and contributed to discussion. H.C. researched data. J.H.A., S.W.K., K.S.P., H.C.J., and S.Y.K. contributed to discussion. C.S.S. had the original idea, contributed to discussion, and reviewed and edited the manuscript.